Copper-catalyzed oxygenation of 3-hydroxy-2-phenylquinolin-4(1H)-one: Synthesis, structure and spectral properties of [Cu(idpa)(N-baa)]ClO 4, [idpa = 3,3′-iminobis(N,N-dimethylpropylamine), N-baaH = N-benzoylanthranilic acid]

Article abstract of DOI:10.1016/j.inoche.2005.06.007

Reaction of one molar equivalent of 3,3′-iminobis(N,N- dimethylpropylamine (idpa)), N-benzoylanthranilic acid (N-baaH) and [Cu(CH ₃CN)₄](ClO₄) in acetonitrile resulted in the formation of a stable ionic copper(II) complex without additional solvent coordination. The composition and molecular structure of [Cu(idpa)(N-baa)] ClO₄ was fully determined by IR, UV-vis, and X-ray crystal analysis. The complex has a distorted square planar CuN₃O core. The oxygenation of 3-hydroxy-2-phenylquinolin-4(1H)-one (QuinH₂) using [Cu(idpa)(N-baa)]ClO₄ as a catalyst results in the oxidative cleavage of the heterocyclic ring to give a N-benzoylanthranilic acid and CO as a mimic of quercetinase and 3-hydroxy-1,4-dihydroquinolin-4-one 2,4-dioxygenase action.

Full text of DOI:10.1016/j.inoche.2005.06.007

Inorganic Chemistry Communications 8 (2005) 813–816
www.elsevier.com/locate/inoche
Copper-catalyzed oxygenation of
3-hydroxy-2-phenylquinolin-4(1H)-one: Synthesis, structure
and spectral properties of [Cu(idpa)(N-baa)]ClO4,
[idpa = 3,30-iminobis(N,N-dimethylpropylamine),
N-baaH = N-benzoylanthranilic acid]
a
b
b
a,b,
*
´
´
´
´
Jozsef Kaizer , Tamas Csay , Miklos Czaun , Gabor Speier
,
c
c
´
Marius Reglier , Michel Giorgi
a
Research Group for Petrochemistry, Hungarian Academy of Sciences at University of Veszpre´m, 8201 Veszpre´m, Hungary
b
Department of Organic Chemistry, University of Veszpre´m, 8201 Veszpre´m, Hungary
c
ˆ
Laboratoire de Cristallochimie et Laboratoire de Bioinorganique Structurale Universite´ Paul Ce´zanne Aix-Marseille III F.S.T. Saint-Je´rome,
Service 432 Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Received 9 May 2005; accepted 2 June 2005
Available online 20 July 2005
Abstract
Reaction of one molar equivalent of 3,30-iminobis(N,N-dimethylpropylamine (idpa)), N-benzoylanthranilic acid (N-baaH) and
[Cu(CH3CN)4](ClO4) in acetonitrile resulted in the formation of a stable ionic copper(II) complex without additional solvent coor-
dination. The composition and molecular structure of [Cu(idpa)(N-baa)]ClO4 was fully determined by IR, UV–vis, and X-ray crys-
tal analysis. The complex has a distorted square planar CuN3O core. The oxygenation of 3-hydroxy-2-phenylquinolin-4(1H)-one
(QuinH2) using [Cu(idpa)(N-baa)]ClO4 as a catalyst results in the oxidative cleavage of the heterocyclic ring to give a N-benzoy-
lanthranilic acid and CO as a mimic of quercetinase and 3-hydroxy-1,4-dihydroquinolin-4-one 2,4-dioxygenase action.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Copper; 3-Hydroxy-2-phenylquinolin-4(1H)-one; N-benzoylanthranilic acid; Dioxygenation; Quercetinase
To date, four prokaryotic dioxygenases are known,
which catalyze an oxidative C–C bond cleavage with
incorporation of two O-atoms into, and release of CO
from their substrate [1–4]. Flavonol 2,4-dioxygenase
(FDO), which catalyzes the cleavage of flavonol (1) to
carbon monoxide and phenolic carboxylic acid ester
(3) was produced by the copper-containing fungi like
Aspergillus flavus [5], Aspergillus niger [6], Aspergillus
japonicus [7] and the iron-containing protein Yxag from
Bacillus subtilis [8]. In the course of model studies of
FDO numerous copper complexes of flavonol and O-
benzoylsalicylic acid have been prepared and character-
ized [9–13]. 3-Hydroxy-2-phenylquinolin-4(1H)-one (2)
QuinH2 which is isoelectronic with flavonol (1) is
degraded by the enzyme 3-hydroxy-1,4-dihydroquino-
lin-4-one 2,4-dioxygenase [2,3]. This enzyme does not
contain any metallic cofactor. The base-catalyzed oxy-
genation of 3-hydroxy-2-phenylquinolin-4(1H)-one as
a functional model showed that these reactions lead to
cleavage products, including 4 and carbon monoxide
[14].
*
Corresponding author. Fax: +36 88 427 492.
E-mail address: speier@almos.vein.hu (G. Speier).
1387-7003/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2005.06.007

814
J. Kaizer et al. / Inorganic Chemistry Communications 8 (2005) 813–816
Ph
X
O
Ph
X
+ CO
+ O2
O
OH
CO2H
X = O
3
4
Flavonol 2,4-dioxygenase
3-hydroxy-1,4-dihydroquinolin-4-one
2,4-dioxygenase
1
X = NH
2
ð1Þ
In this communication, we present the synthesis and
structural characterization of a new ionic (N-benzoy-
lanthranilato)copper(II) complex with a tridentate li-
gand 3,30-iminobis(N,N-dimethylpropylamine) (idpa)
[Cu(N-baa)(idpa)]ClO4 (5), obtained with practically
quantitative yield by interaction of [Cu(CH3CN)4]ClO4,
N-benzoylanthranilic acid, and idpa in acetonitrile un-
der dioxygen atmosphere [15]. The determination of its
structure was carried out by X-ray single crystal study.
In addition IR and UV–vis analysis of the title com-
pound and its dioxygenase-like activity in the oxygena-
tion of 3-hydroxy-2-phenylquinolin-4(1H)-one was also
examined in order to get insight into the mechanism of
these curious reactions.
Complex 5 isolated as a blue solid is stable in air and
analyzed satisfactorily for C, H, N. The infrared (IR)
spectrum of the complex shows bands corresponding
to the coordinated N-benzoylanthranilate at 3438
m(NH), 1670 m(CO), 1593, 1390 m(CO2) and 1303
m(NH) cmꢀ1. The difference between the asymmetric
and symmetric stretching frequencies of the carboxylato
group [Dm = mas(CO2) ꢀ ms(CO2)] is 203 cmꢀ1, rendering
these to a monodentate carboxylate bonding mode
[16,17]. The middle band at 3219 cmꢀ1 can be rendered
to the m(NH) of the 3,30-iminobis(N,N-dimethylpropyl-
amine) ligand. The absorption bands at 1114, 1061
and 624 cmꢀ1 can be assigned to the perchlorate anion.
The electronic spectrum of complex 5 shows an absorp-
tion band at 695 nm due to d–d transition. A higher en-
ergy band at 320 nm is associated with charge transfer
transition. These spectral features are comparable with
those of the [Cu(O-bs)(idpa)]ClO4, (O-bsH = O-benzoyl-
salicylic acid) [18].
Fig. 1. Molecular structure of [Cu(N-baa)(idpa)]+(5) with crystallo-
graphic numbering. Hydrogen atoms are omitted for clarity. Relevant
˚
bond lengths (A) and angles (ꢁ): Cu(1)–N(2) 1.994(2), Cu(1)–N(3)
2.073(3), Cu(1)–N(4) 2.063(3), Cu(1)–O(3) 1.949(2), O(3)–C(14)
1.265(4), C(14)–O(2) 1.246(4), N(1)–C(7) 1.354(4), N(1)–C(1)
1.393(4), C(7)–O(1) 1.223(3). O(3)–Cu(1)–N(2) 152.42(9), N(3)–
Cu(1)–N(4) 138.22(11), O(3)–Cu(1)–N(4) 93.27(10), O(3)–Cu(1)–N(3)
95.72 (12), N(3)–Cu(1)–N(2) 95.97(11), O(2)–C(14)–O(3) 120.0(3),
Cu(1)–O(3)–C(14) 102.75(19). The molecule is monomeric in the solid
state. The overall geometry around the four-coordinate copper ion is
described as an distorted square planar geometry. Three nitrogen
atoms of the tridentate ligand idpa and the oxygen atom of the
monodentate carboxylate group occupy basal positions. The Cu–O
˚
˚
bond distance 1.949 A and Cu–N bond distances average 2.04 A,
which are in the normal range [11,18].
obtained. 3-Hydroxy-2-phenylquinolin-4(1H)-one exhib-
its absorption at 372 nm. Spectral changes accompany-
ing addition of dioxygen to the reaction mixture show
that the absorption peak at 372 nm decrease, while that
at 417 nm increase with time (Fig. 2).
Suitable crystals of 3 were obtained by slow diffusion
of diethyl ether into DMF solution of the complex at
20 ꢁC. The molecular structure of [Cu(N-baa)(idpa)]-
ClO4 [19] as well as selected bond lengths and angles
are shown in Fig. 1.
The reaction between 3-hydroxy-2-phenylquinolin-
4(1H)-one and dioxygen in the presence of catalytic
amounts of [Cu(N-baa)(idpa)]ClO4 were performed in
DMF solutions and examined at 130 ꢁC with a ratio be-
tween initial concentration of [Cu(N-baa)(idpa)]ClO4 (5)
and 3-hydroxy-2-phenylquinolin-4(1H)-one (2) from
1:10 to 1:90. We found that the oxygenation of QuinH2
results in oxidative cleavage of the heterocyclic ring to
give N-benzoylanthranilic acid (4) and CO as products
[22]. The oxidation is selective, no other products were
Fig. 2. Spectral changes accompanying the [Cu(N-baa)(idpa)]ClO4-
catalyzed oxygenation of QuinH2. [[Cu(N-baa)(idpa)]ClO4]0 =
2.67 · 10ꢀ5 M; [QuinH2]0 = 2.4 · 10ꢀ3 M, under dioxygen at 130 ꢁC
in 50 cm3 DMF.

J. Kaizer et al. / Inorganic Chemistry Communications 8 (2005) 813–816
815
[6] H.-K. Hund, J. Breuer, F. Lingens, J. Huttermann, R. Kappl, S.
¨
2
1
0
Fetzner, Eur. J. Biochem. 263 (1999) 871.
[7] F. Fusetti, K.H. Schro¨ter, R.A. Steiner, P.I. van Nort, T. Pijning,
H.J. Rozeboom, K.H. Kalk, M.R. Egmond, B.W. Dijkstra,
Structure 10 (2002) 259.
372 nm
[8] B. Gopal, L.L. Madan, S.F. Betz, A.A. Kossiakoff, Biochemistry
A
B
44 (2005) 193.
´
[9] E. Balogh-Hergovich, J. Kaizer, G. Speier, G. Argay, L. Pa´rka´nyi,
J. Chem. Soc., Dalton Trans. (1999) 3847.
´
´
´
[10] E. Balogh-Hergovich, J. Kaizer, G. Speier, V. Fulo¨p, L. Parkanyi,
¨
417 nm
Inorg. Chem. 38 (1999) 3787.
´
[11] E. Balogh-Hergovich, J. Kaizer, G. Speier, G. Huttner, A. Jacobi,
Inorg. Chem. 39 (2000) 4224.
´
´
[12] J. Kaizer, J. Pap, G. Speier, L. Parkanyi, Eur. J. Inorg. Chem.
0
100
200
Time/s
300
400
500
(2004) 2253.
´
[13] E. Balogh-Hergovich, J. Kaizer, J. Pap, G. Speier, G. Huttner, L.
Fig. 3. Spectral changes accompanying the [Cu(N-baa)(idpa)]ClO4-
Zsolnai, Eur. J. Inorg. Chem. (2002) 2287.
catalyzed oxygenation of QuinH2 at 372 and 417 nm. [[Cu
[14] M. Czaun, G. Speier, Tetrahedron Lett. 43 (2002) 5961.
[15] Synthesis of [Cu(idpa)(N-baa)]ClO4: [Cu(CH3CN)4]ClO4 (0.328 g,
1 mmol), N-benzoylanthranilic acid (0.241 g, 1 mmol) and 3,30-
iminobis(N,N-dimethylpropylamine) (0.186 g, 1 mmol) were dis-
solved in 20 cm3 of acetonitrile and refluxed under dioxygen for
6 h. The product was collected by filtration, washed with diethyl
ether and dried in vacuum (0.53 g, 90%). M.p. 183–187 ꢁC. IR
(KBr) cmꢀ1: 3438 m, 3219 m, 3144 w, 3101 w, 2939 w, 2880 w,
1670 s, 1593 s, 1505 vs, 1452 m, 1390 vs, 1303 s, 1260 m, 1114 vs,
1061 s, 1043 s, 899 w, 863 w, 829 w, 761 m, 713 m, 624 s, 590 w,
538 w, 455 w. UV–vis (DMF) kmax ðlog e=dm3 molꢀ1 cmꢀ1Þ: 320
(3.92); 695 (2.50). Anal. Calc. For C24H35ClCuN4O7: C, 48.81; H,
5.97; N, 9.49. Found: C, 48.31; H, 6.05; N, 9.23%.
(N-baa)(idpa)]ClO4]0 = 2.67 · 10ꢀ5 M;
[QuinH2]0 = 2.4 · 10ꢀ3 M,
under dioxygen at 130 ꢁC in 50 cm3 DMF.
Plots of the time dependence of the absorptions show
two segments, indicating that there are at least two pro-
cesses occurring consecutively [23]. The initial gradient
(part A) hints to a slower process, while the second
one (part B) may be considered as the actual oxygena-
tion process of the coordinated 3-hydroxy-2-phenyl-
quinolin-4(1H)-one ligand (Fig. 3). The first one is
believed to correspond to a slow conversion of the
[Cu(N-baa)(idpa)]ClO4 to [Cu(idpa)(QuinH)]ClO4,
which then reacts with dioxygen to the end-product.
This reaction resembles the enzyme action on 3-hydroxy-
2-phenylquinolin-4(1H)-one to give the cleavage product
as shown earlier (Eq. (1)).
[16] G. Christou, S.P. Perlepes, E. Libby, K. Folting, J.C. Huffman,
R.J. Webb, D.N. Hendrickson, Inorg. Chem. 29 (1990) 3657.
[17] I. Chadjistamatis, A. Terzis, C.P. Raptopoulou, S.P. Perlepes,
Inorg. Chem. Commun. 6 (2003) 1365.
´
[18] E. Balogh-Hergovich, J. Kaizer, G. Speier, G. Huttner, L.
Zsolnai, Inorg. Chim. Acta 304 (2000) 72.
[19] Crystal data for 2: C24H35ClCuN4O7, 590.55 g molꢀ1, monoclinic,
˚
˚
˚
P21/c, a = 12.7890(2) A, b = 12.0840(1) A, c = 17.8870(2) A, b =
3
˚
93.6500(5) (ꢁ), Z = 4, V = 2758.69(6) A , l(Mo Ka) =
0.937 mmꢀ1, dcalc = 1.422 g cmꢀ3, T = 293(2) K, F(000) = 1236.
The intensity data were collected with a Nonius Kappa CCD
single-crystal diffractometer using Mo Ka radiation (k = 0.71073).
Reflections collected = 21473, reflections total = 5340, reflections
unique = 4764. The structure was refined to R = 0.0465 (0.0529)
and wR2 = 0.1267 for the reflections with I > 2r(I) (all data) and
Acknowledgement
Financial support of the Hungarian National
Research Fund (OTKA T-043414) is gratefully
acknowledged.
max. resd. density = 0.487e Aꢀ3. The computer program used
˚
were SHELXL97 [20]. The structure was solved by direct and
difmap methods (SIR92) [21]. CCDC reference number: 271100.
[20] G.M. Sheldrick, SHELXL97. Program for the Refinement of
Crystal Structures, University of Go¨ttingen, Germany, 1997.
[21] A. Altamore, G. Cascarano, C. Giacovazzo, A. Guagliardi, M.C.
Burla, G. Polidori, M.J. Camalli, J. Appl. Cryst. 27 (1994) 435.
[22] [Cu(idpa)(N-baa)]ClO4-catalyzed oxygenation of 3-hydroxy-2-
Appendix A. Supplementary data
Supplementary data associated with this article can
be found, in the online version at doi:10.1016/
j.inoche.2005.06.007.
phenylquinolin-4(1H)-one:
3-hydroxy-2-phenylquinolin-4(1H)-
one (0.0360 g, 0.15 mmol) and [Cu(idpa)(N-baa)]ClO4 (0.0044 g,
0.0075 mmol) were dissolved and stirred at 130 ꢁC in 5 cm3 DMF
for 12 h under dioxygen atmosphere. Diazomethane solution
(2 cm3 ) (in diethyl ether) was added to 0.5 cm3 of the reaction
mixture at r.t. and the conversion (75%) of 3-hydroxy-2-phenyl-
quinolin-4(1H)-one into N-benzoylanthranilic acid was deter-
mined by GC as the methylated derivative.
References
[1] S. Hattori, I. Noguchi, Nature 184 (1959) 1145.
[2] I. Bauer, A. de Beyer, B. Tshisuaka, S. Fetzner, F. Lingens, FEMS
Microbiol. Lett. 117 (1994) 299.
[3] I. Bauer, N. Max, S. Fetzner, F. Lingens, Eur. J. Biochem. 240
(1996) 576.
[4] J.W. Wray, R.H. Abeles, J. Biol. Chem. 268 (1993) 24785.
[5] T. Oka, F.J. Simpson, Biochem. Biophys. Res. Commun. 43
(1971) 1.
[23] The [Cu(idpa)(N-baa)]ClO4-catalyzed oxygenation of 3-hydroxy-
2-phenylquinolin-4(1H)-one was followed by UV–vis spectroscopy
too. In a typical experiment 3-hydroxy-2-phenylquinolin-4(1H)-
one and [Cu(idpa)(N-baa)]ClO4 was dissolved under argon
atmosphere in a thermostated reaction vessel with an inlet for
taking samples with
a syringe, and connected to mercury

816
J. Kaizer et al. / Inorganic Chemistry Communications 8 (2005) 813–816
manometer to regulate constant dioxygen pressure. The solution
was then heated to appropriate temperature and the argon was
replaced by dioxygen. The concentration of 3-hydroxy-2-phenyl-
quinolin-4(1H)-one was determined by measuring the absorbance
of the reaction mixture at 372 nm (log e 3.96) (kmax of a typical
band of 3-hydroxy-2-phenylquinolin-4(1H)-one).